Twenty-year study proves tamoxifen saves lives

The latest results from the International Breast Cancer Intervention Study – one of the longest studies of its kind – show a nearly 30% reduction in the incidence of disease when women at an elevated risk for developing breast cancer are treated prophylactically with the anti-oestrogen drug tamoxifen.

"After 20 years of follow-up, there is a clear benefit in terms of preventing breast cancer with this agent,” said the lead investigator on the IBIS-1 study, Jack Cuzick of Queen Mary University, London, reporting results at the recent San Antonio Breast Cancer Conference.

The study findings are considered remarkable on two fronts, first, that the incidence of breast cancer can be prevented with anti-oestrogen treatment, and second, that these observations could be successfully carried out over such a long period of time.

Beginning in 1992, and lasting through mid-2001, IBIS-1 investigators enrolled 7,154 women previously identified as having an elevated risk for developing breast cancer. Patients were randomised to one of two treatment arms, receiving either tamoxifen, or placebo, for five years, and then followed up for as long as possible.

“What is important about this particular analysis is we now have very long-term follow-up,” said Dr Cuzick, “The median follow-up is 16 years, and many patients have been followed for twenty or more years.”

The average age of patients at study entry was around 50, the cohort was split between pre-menopausal and post-menopausal women, and, of particular interest, roughly half of those individuals enrolled used hormone replacement therapy while on study.

“That is one of the important features of the study, that we did allow HRT use during the trial, and about half of the women did use that, and that turns out to be important in terms of outcome.”

Overall, with median 16-years of follow-up, study results showed that five years of treatment with tamoxifen resulted in a 29% reduction in the occurrence of breast cancer: there were 251 cases observed in the tamoxifen treatment arm, as compared to 350 cases in the placebo group.

“These data suggest that the number of patients you need to treat to prevent one new case of breast cancer is 22,” Dr Cuzick said, “Which is very favourable as compared to any preventative treatment, say, for heart disease or anything else in the general population.”

As for the significance of HRT, a sub-analysis of the IBIS-1 cohort showed that the preventative effect offered by tamoxifen is attenuated by HRT use during the active treatment period.

The benefit of tamoxifen was not without some physical cost; there was a small (but expected) increase reported for the incidence of endometrial cancer in the active treatment arm: 29 cases vs 20 cases in the placebo group. And, oddly, there was in increase in non-melanoma (low mortality) skin cancer: 116 cases vs 84 for tamoxifen and placebo, respectively.

“This was a somewhat unexpected event,” said Dr Cuzick, “It raises the question as to whether there is any mechanism through which tamoxifen might be causing these cancers, but right now we just don’t know.”

“I think we have to recognise that breast cancer is truly the epidemic of our century,” Dr Cuzick concluded. “Rates are dramatically higher than any other cancer type in women, at 1.6 million cases per year worldwide. And these numbers are rising so treatment is really not enough, we have to really get the incidence of this disease down.”